Transcript Organic Chemistry I

Organic Chemistry
Mario Lintz
[email protected]
303-946-5838
1
Organic Chemistry I
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Functional Groups
Molecular Structure
Hydrocarbons
Substitution and Elimination
Oxygen Containing Compounds
Amines
2
Functional Groups
List #1- Critical for the MCAT
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Alkane
Alkene
Alkyne
Alcohol
Ether
Amine
Aldehyde
Ketone
Carboxylic Acid
Ester
Amide
3
Functional Groups
List #2- Memorize as well
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Alkyl
Halogen
Gem-dihalide
Vic dihalide
Hydroxyl
Alkoxy
Hemiacetal
Hemiaketal
Mesyl group
Tosyl group
Carbonyl
Acetal
Acyl
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Anhydride
Aryl
Benzyl
Hydrazine
Hydrazone
Vinyl
Vinylic
Allyl
Nitrile
Epoxide
Enamine
Imine
Nitro
Nitroso
4
5
Bonds
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Types:
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Ionic: complete transfer of electrons
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Covalent: shared electrons
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Coordinate covalent bonds- One atom provides both
electrons in a shared pair.
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Polar covalent: unequal sharing of electrons
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Hydrogen Bonds: bonds between polar molecules
containing H and O, N, or F
6
Bonds
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A.
B.
C.
D.
In the pi bond of an alkene, the electron pair have:
33% p character and are at a lower energy level
than the electron pair in the o bond.
33% p character and are at a higher energy level
than the electron pair in the o bond.
100% p character and are at a lower energy level
than the electron pair in the o bond.
100% p character and are at a higher energy level
than the electron pair in the o bond.
7
Covalent Bonds
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Sigma s
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Pi P
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Covalent Bonds
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Sigma s
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Between s orbitals
Small, strong, lots of rotation
Pi P
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Covalent Bonds
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Sigma s
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Between s orbitals
Small, strong, lots of
rotation
Pi P
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Between p orbitals
Discreet structure,
weaker than sigma, no
rotation
10
Covalent Bonds
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Sigma s
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Between s orbitals
Small, strong, lots of
rotation
Pi P
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Between p orbitals
Discreet structure,
weaker than sigma, no
rotation
Always add to sigma
bonds creating a
stronger bond
11
When albuterol I dissolved in water, which of the
following hydrogen-bonded structures does NOT
contribute to its water solubility?
12
Dipole Moments
(Solely responsible for Intermolecular Attractions)
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Charge distribution of bond is unequal
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Induced Dipoles
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Due to random e- movement
Hydrogen Bonds
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Spontaneous formation of dipole moment in nonpolar molecule
Occurs via: polar molecule, ion, or electric field
Instantaneous Dipole
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Molecule with dipole moment = polar
Molecule without dipole moment = nonpolar
Possible to have nonpolar molecules with polar bonds
Strongest dipole-dipole interaction
Responsible for high BP of water
London Dispersion Forces
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Between 2 instantaneous dipoles
Responsible for phase change of nonpolar molecules
13
Lewis Dot Structures
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Rules for writing
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Exceptions
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Find total # valence e1 e- pair = 1 bond
Arrange remaining e- to satisfy duet and octet rules
Atoms containing more than an octet must come from the
3rd period, (vacant d orbital required for hybridization)
 Not very popular on the MCAT
Formal Charge
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# valence e- (isolated atom) - # valence e- (lewis structure)
Sum of formal charge for each atom is the total charge on
the molecule
 (actual charge distribution depends on electronegativity)
14
Structural Formulas
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Dash Formula
Condensed Formula
Bond-line Formula
Fischer projection
Newman projection
Dash-line-wedge
Ball and stick
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All Images courtesy of Exam Krackers
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15
Hybridization
16
Hybrid Bonds
Suffix
C bonds
Hybridiz
ation
Percent
S:P
Bond
Angle
Bond
Length
Bond
Strength
-ane
-ene
-yne
-yl
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Hybrid Bonds
Suffix
C bonds
Hybridiz
ation
Percent
Bond
Angleo
Bond
Length
(pm)
Bond
Strength
(kJ/mol)
S:P
-ane
C-C
sp3
25:75
109.5
154
346
-ene
C=C
sp2
33:66
120
134
612
-yne
C=C
sp
50:50
180
120
835
-yl
Side
chain
18
Hybrid Bonding in Oxygen and
Nitrogen
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Nitrogen
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Lone pair occupies more space than N-H
Causes compression of the bond angle. Bond
angles are 107.3 as opposed to 109.5
Oxygen
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2 sets of lone pair electrons
Causes greater compression than in Nitrogen.
H2O bond angles are 104.5 vs 109.5.
19
For the molecule 1,4 pentadiene, what
type of hybridization is present in
carbons # 1 and # 3 respectively?
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A) sp2, sp2
B) sp2, sp3
C) sp3, sp3
D) sp3, sp2
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VSEPR
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valance shell electron pair repulsion
Prediction of shape
Minimize electron repulsion
1. Draw the Lewis dot structure for the molecule or
ion
2. Place electron pairs as far apart as possible, then
large atoms, then small atoms
3. Name the molecular structure based on the
position of the atoms (ignore electron pairs)
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21
VSEPR
1. Draw the Lewis dot structure for the molecule or ion
2. Place electron pairs as far apart as possible, then large atoms, then small
atoms
3. Name the molecular structure based on the position of the atoms (ignore
electron pairs)
molecule
BeCl2
Lewis structure
Shape
molecule
Lewis structure
Shape
Linear, sp
SF4
Seesaw
SO3
Trigonal
planar,
sp2
ICl3
T shaped
NO2-
Bent
CH4
Tetrahedral,
sp3
NH3
Trigonal
Pyramid
al
PCl5
Trigonal
bipyramidal,
dsp3
SF6
Octahed
ral,
d2sp3
IF5
Square
Pyramidal
ICl4-
Square
Planar
22
Delocalized e- and Resonance
passage 25
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Resonance forms differ only in the placement of
pi bond and nonbonding eDoes not suggest that the bonds alternate
between positions
Neither represent the actual molecule, rather the
real e assignment is the intermediate of the
resonant structures. The real structure is called a
resonance hybrid (cannot be seen on paper)
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Organic Acids and Bases
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Organic Acids- Presence of positively charged H+
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Two kinds
 present on a OH such as methyl alcohol
 present on a C next to a C=O such as acetone
Organic Bases- Presence of lone pair e to bond to H
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Nitrogen containing molecules are most common
Oxygen containing molecules act as bases in presence of
strong acids
24
Stereochemistry
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Isomers: same elements, same proportions.
Different spatial arrangements => different
properties.
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Structural (constitutional): Different connectivity.
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Isobutane vs n-butane
Both C4H10
Conformational (rotational): Different spatial
arrangement of same molecule
 Chair vs. boat
 Gauche vs Eclispsed vs Antistaggered vs Fully
Eclipsed
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Stereochemistry-isomers
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Stereoisomers: different 3D arrangement
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Enantiomers: mirror images, nonsuperimposable.
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Same physical properties (MP, BP, density, solubility,
etc.) except rotation of light and reactions with other
chiral compounds
May function differently; e.g. thalidomide, sugars, AA
Have chiral centers
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Stereochemistry-isomers
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Stereoisomers: different 3D arrangement
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Diastereomers: not mirror images (cis/trans)
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Different physical properties (usually),
Can be separated
Chiral diastereomers have opposite configurations at
one or more chiral centers, but have the same
configuration at others.
27
Stereochemistry-isomers
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What kind of isomers are the two compounds below?
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A. Configurational diastereomers
B. Enantiomers
C. Constitutional isomers
D. Cis -trans diastereomers
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28
Stereochemistry-polarization
of light
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Excess of one enantiomer causes rotation of plane-polarized light.
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Right, clockwise, dextrarotary (d), or +
Left, counterclockwise, levarotary (l), or –
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Racemic: 50:50 mixture of 2 enantiomers, no net rotation of light
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RELATIVE Configuration: configuration of one molecule relative to
another. Two molecules have the same relative configuration
about a carbon if they differ by only one substituent and the
other substituents are oriented identically about the carbon.
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Specific rotation [a]: normalization for path length (l) and sample density
(d). ocm3/g
[a] = a / (l*d)
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Stereochemistry-Chiral molecules
passage 27
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Achiral=plane or center of symmetry
ABSOLUTE Configuration: physical orientation of atoms
around a chiral center
R and S:
1. Assign priority, 1 highest, 4 lowest
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H < C < O < F higher atomic #, higher priority
If attachments are the same, look at the b atoms (ethyl beats
methyl)
2. Orient 4 away from the observer
3. Draw a circular arrow from 1 to 2 to 3
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R = clockwise
S = counterclockwise
 This has nothing to do with the rotation of light!
E and Z: Different than cis and trans
 Z= same side of high priority groups
 E=opposite side of high priority groups
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IUPAC Naming Conventions
IUPAC Rules for Alkane Nomenclature
1. Find and name the longest continuous carbon
chain.
2. Identify and name groups attached to this chain.
3. Number the chain consecutively, starting at the end
nearest a substituent group.
4. Designate the location of each substituent group by
an appropriate number and name.
5. Assemble the name, listing groups in alphabetical
order. The prefixes di, tri, tetra etc., used to
designate several groups of the same kind, are not
considered when alphabetizing.
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Hydrocarbons
# of C
Root Name
# of C
Root Name
1
meth
6
hex
2
eth
7
hept
3
prop
8
oct
4
but
9
non
5
pent
10
dec
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Hydrocarbons
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Saturated: CnH(2n+2)\
Unsaturated: CnH[2(n-u+1)] ; u is
the # of sites of unsaturation
Primary, secondary, tertiary, and
quaternary carbons
Know and be able to recognize
the following structures
n-butyl
sec-butyl
n-propyl
iso-butyl
tert-butyl
Iso-propyl
33
Alkanes
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Physical Properties:
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Straight chains: MP and BP increase with length
(increased van Der Waals interactions)
 C1-4: gas
 C5-17: liquid
 C18+: solid
Branched chains:
 BP decreases (less surface area, fewer vDW)
 When compared to the straight chain analog, the straight
chain will have a higher MP than the branched molecule.
BUT, amongst branched molecules, the greater the
branching, the higher the MP.
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Alkanes-Important Reactions
Very Unreactive
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Combustion:
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Alkane + Oxygen + High energy input (fire)
Products: H2O, CO2, Heat
Halogenation
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Initiation with UV light
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Propagation (chain reaction mechanisms)
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Homolytic cleavage of diatomic halogen
Yields a free radical
Halogen radical removes H from alkyl
Yields an alkyl radical
Termination
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Radical bonds to wall of container or another radical
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Reactivity of halogens: F > Cl > Br >>> I
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Selectivity of halogens (How selective is the halogen in choosing a position on an alkane):
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I > Br > Cl > F
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more electronegative (Cl) means less selective (Br)
Stability of free radicals: more highly substituted = more stable
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aryl>>>alkene> 3o > 2o > 1o >methyl
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Halogenation
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A.
B.
C.
D.
In the halogenation of an alkane, which of the
following halogens will give the greatest percent
yield of a tertiary alkyl halide when reacted with 2methylpentane in the presence of UV light.
F2
Cl2
Br2
2-methylpentane will not yield a tertiary product
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Cycloalkanes
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General formula: (CH2)n or CnH2n
As MW increases BP increases though MP
fluctuates irregularly because different shapes of
cycloalkanes effects the efficiency in which
molecules pack together in crystals.
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Ring strain in cyclic compounds:
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Bicyclic Molecules:
37
http://www.chem.uh.edu/Courses/Thummel/Chem3331/Notes/Chap3/
Cycloalkanes
Naming
Find parent
Count C’s in ring vs longest chain. If # in ring is equal to or
greater than chain, then name as a cycloalkane.
Number the substituents and write the name
Start at point of attachment and number so that subsequent
substituents have the lowest # assignment
If two or more different alkyl groups are present, number them
by alphabetic priority
If halogens are present, treat them like alkyl groups
Cis vs Trans
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Think of a ring as having a top and bottom
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If two substituents both on top: cis
It two substituents and 1 top, 1 bottom: trans
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Cycloalkanes
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Ring Strain
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Zero for cyclohexane (All C-C-C bond angles: 111.5°)
Increases as rings become smaller or larger (up to cyclononane)
Cyclohexane
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Exist as chair and boat conformations
Chair conformation preferred because it is at the lowest energy.
Hydrogens occupy axial and equatorial positions.
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Axia (6)l- perpendicular to the ring
Equatorial (6)- roughly in the plane of the ring
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Neither energetically favored
When the ring reverses its conformation, substituents reverse their
conformation
Substituents favor equatorial positions because crowding occurs most
often in the axial position.
39
Cyclohexanes
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In a sample of cis-1,2-dimethylcyclohexane
at room temperature, the methyl groups will:
A.
B.
C.
D.
Both be equatorial whenever the molecule is in the
chair conformation.
Both be axial whenever the molecule is in the chair
conformation.
Alternate between both equatorial and both axial
whenever the molecule is in the chair conformation
Both alternate between equatorial and axial but will
never exist both axial or both equatorial at the same
time
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Substitutions
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Substitution: one functional group replaces
another
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Electrophile: wants electrons, has partial + charge
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Nucleophile: donates electrons, has partial – charge
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Substitution
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SN1: substitution, nucleophilic, unimolecular
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Rate depends only on the substrate (i.e. leaving group)
R=k[reactant]
Occurs when Nu has bulky side groups, stable carbocation
(3o), weak Nu (good leaving group)
Carbocation rearrangement
Two step reaction
 1. spontaneous formation of
carbocation (SLOW)
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2. Nucleophile attacks carbocation
(chiral reactants yield racemic
product mixtures)
42
Substitution
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SN2: substitution, nucleophilic, bimolecular
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Rate depends on the substrate and the nucleophile
R=k[Nu][E]
Inversion of configuration
Occurs with poor leaving groups (1o or 2o)
One step reaction
 1. Nu attacks the C with a
partial + charge
http://www.mhhe.com/physsci/chemistry/carey5e/Ch08/ch8-4.html
43
Which of the following
carbocations is the most stable?
A
. CH3CH2CH2CH2
B
. CH3CH2CH2CHCH3
C
. (CH3)3C
D
. CH3
44
Benzene
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Undergoes substitution not addition
Flat molecule
Stabilized by resonance
Electron donating groups activate the ring and are ortho-para
directors
Electron withdrawing groups deactivate the ring and are meta
directors
Halogens are electron withdrawing, however, are ortho-para
directors
45
Benzene
Substituent Effects
46
Oxygen Containing
Compounds
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Alcohols
Aldehydes and Ketones
Carboxylic Acids
Acid Derivatives
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Acid Chlorides
Anhydrides
Amides
Keto Acids and Esters
47
Alcohols
One of the most common reactions of alcohols is
nucleophilic substitution. Which of the following
are TRUE in regards to SN2 reactions:
Inversion of configuration occurs
Racemic mixture of products results
Reaction rate = k [S][nucleophile]
I.
II.
III.
A.
B.
C.
D.
I only
II only
I and III only
I, II, and III
48
Alcohols
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Physical Properties:
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Polar
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High MP and BP (H bonding)

More substituted = more basic
 (CH3)3COH:
pKa = 18.00
 CH3CH2OH:
pKa = 16.00
 CH3OH:
pKa = 15.54
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Electron withdrawing substituents stabilize alkoxide ion and lower pKa.
 Tert-butyl alcohol:
pKa = 18.00
 Nonafluoro-tert-butyl alcohol:
pKa = 5.4
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IR absorption of OH at ~3400 cm-
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General principles
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H bonding

Acidity: weak relative to other O containing compounds
(CH groups are e- donating = destabilize deprotonated species)
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Branching: lowers BP and MP
49
Alcohols
Naming
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Select longest C chain containing the hydroxyl
group and derive the parent name by
replacing –e ending of the corresponding
alkane with –ol.
Number the chain beginning at the end
nearest the –OH group.
Number the substituents according to their
position on the chain, and write the name
listing the substituents in alphabetical order.
50
Alcohols-Oxidation & Reduction
Oxidation
51
Reduction
Alcohols-Oxidation & Reduction
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Common oxidizing and reducing agents
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Generally for the MCAT
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Oxidizing agents have lots of oxygens
Reducing agents have lots of hydrogens
Oxidizing Agents
K2Cr2O7
KMnO4
H2CrO4
O2
Br2
Reducing Agents
LiAlH4
NaBH4
H2 + Pressure
52
Reduction Synthesis of
Alcohols
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
Reduction of aldehydes, ketones, esters, and
acetates to alcohols.
Accomplished using strong reducing agents such as
NaBH4 and LiAlH4
Electron donating groups increase the negative
charge on the carbon and make it less susceptible to
nucleophilic attack.


Reactivity:
 Aldehydes>Ketones>Esters>Acetates
Only LiAlH4 is strong enough to reduce esters and
acetates
53
Alcohols: Pinacol
rearrangement
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Starting with Vicinal Diol
Generate ketones and aldehydes
Formation of most stable carbocation
Can get ring expansion or contraction
http://www.cem.msu.edu/~reusch/VirtualText/rearrang.htm
54
Alcohols-Protection



Alcohol behaves as the nucleophile. (As is
often the case)
OH easily transfer H to a basic reagent, a
problem in some reactions.
Conversion of the OH to a removable
functional group without an acidic proton
protects the alcohol
55
http://www.chem.umd.edu/courses/spring05/chem241fribush/chsum/354,60,Protection-Deprotection
56
Alcohols to Alkylhalides
via a strong acid catalyst

R-OH + HCl  RCl + H20

Alcohol is protonated by strong acid, (it takes a
strong acid to protonate an alcohol).
-OH is converted to the much better leaving group,
H2O
Occurs readily with tertiary alcohols via treatment
with HCl or HBr.
Primary and secondary alcohols are more resistant
to acid and are best converted via treatment with
SOCl2 or PBr3



57
Alcohols to Alkylhalides
reactions with SOCl2 and PBr3




Halogenation of alcohols via SN1 or SN2
OH is the Nu, attacking the halogenating agent
It is not OH that leaves, but a much better leaving
group -OSOCl or –OPBr2, which is readily expelled
by backside nucleophilic substitution.
Does not require strong acids (HCl, HBr)
58
Alcohols-preparation of
mesylates and tosylates



OH is a poor leaving
group, unless protonated,
but most Nu are strong
bases and remove such a
proton
Conversion to mesylates
or tosylates allow for
reactions with strong Nu
Preparation SN1: no
change of stereogenic
center. Reaction SN2:
inversion of configuration
http://www.oglethorpe.edu/faculty/~m_wolf/PowerPoint/CareyOrgPP/sections
1st/380,36,Tosylates allow control of stereochemistry and
59
http://www.chem.uh.edu/Courses/Thummel/Chem3331/Wade/wade11.pdf
Alcohols: Esterification

Fischer Esterification Reaction:

Alcohol + Carboxylic Acid  Ester + Water


Acid Catalyzed- protonates –OH to H2O (excellent
leaving group)
Alcohol performs nucleophilic attack on carbonyl
carbon
These bonds are
broken
60
Alcohols: Inorganic Esters
passage 30
Esters with another atom in place of the
carbon
1. Sulfate esters: alcohol + sulfuric acid
2. Nitrate esters: alcohol + HNO3 (e.g.
nitroglycerine)
 3. Phosphate esters: DNA

61
Upon heating 2,3-Dimethyl-2,3-butanediol
with aqueous acid, which of the following
products would be obtained in the greatest
amount?
a) 3,3-Dimethyl-2-butanone
b) 2,2-Dimethyl-3-butanone
c) 2,3-Dimethyl-3-butanone
d) 2,3-Dimethyl-2-butanone

62
In the reaction above, what is the purpose of
using the 1,2-ethanediol in the first step?
a) Heterogeneous catalyst
b) Homogeneous catalyst
c) Alcohol protection
d) Oxidizing agent

63
In the reaction above, if the reagents in the
first step were replaced with LiAlH4, what
product would result?
O
OH
a)
c)

OH
b)
OH
OH
d)
OH
HO
OH
64
Carbonyls
Carbon double bonded to Oxygen





Planar stereochemistry
Partial positive charge on Carbon
(susceptibility to nucleophilic attack)
Aldehydes & Ketones (nucleophilic addition)
Carboxylic Acids (nucleophilic substitution)
Amides
65
Aldehydes and Ketones

Physical properties:




Carbonyl group is polar
Higher BP and MP than alkanes because of dipole-dipole interactions
More water soluble than alkanes
Trigonal planar geometry, chemistry yields racemic mixtures

IR absorption of C=O at ~1600

General principles:




Effects of substituents on reactivity of C=O: e- withdrawing increase
the carbocation nature and make the C=O more reactive
Steric hindrance: ketones are less reactive than aldehydes
Acidity of alpha hydrogen: carbanions
a, b unsaturated carbonyls-resonance structures
66
Aldehydes and Ketones
Naming

Naming Aldehydes





Replace terminal –e of corresponding alkane with –al.
Parent chain must contain the –CHO group
The –CHO carbon is C1
When –CHO is attached to a ring, the suffix carbaldehyde
is used.
Naming Ketones



Replace terminal –e of corresponding alkane with –one.
Parent chain is longest chain containing ketone
Numbering begins at the end nearest the carbonyl C.
67
Aldehydes and KetonesAcetal and Ketal Formation
nucleophilic addition at C=O bond
68
Aldehydes and KetonesImine Formation
nucleophilic addition at C=O bond

Imine R2C=NR


Primary amines (RNH2) + aldehyde or ketone  R2C=NR
Acid Catalyzed protonation of –OH  H2O
69
Aldehydes and KetonesEnamine Formation
nucleophilic addition at C=O bond

Enamine (ene + amine) R2N-CR=CR2


Secondary amine (R2N) + aldehyde or ketone  R2NCR=CR2
Acid catalyzed protonation of –OH  H2O
70
Aldehydes and Ketonesreactions at adjacent positions

Haloform: trihalomethane


Halogens add to ketones at the alpha position in
the presence of a base or acid.
Used in qualitative analysis to indicate the
presence of a methyl ketone. The product,
iodoform, is yellow and has a characteristic odor.
71
Aldehydes and Ketonesreactions at adjacent positions

Aldol (aldehyde + alcohol) condensation:




Occurs at the alpha carbon
Base catalyzed condensation
Alkoxide ion formation (stronger than –OH, extracts H from H2O to
complete aldol formation)
Can use mixtures of different aldehydes and ketones
72
Aldehydes and Ketones-Oxidation
(Aldehydes  Carboxylic acids)

Aldehydes are easy to oxidize because of the
adjacent hydrogen. In other words, they are good
reducing agents.




Potassium dichromate (VI): orange to green
Tollens’ reagent (silver mirror test): grey ppt.
 Prevents reactions at C=C and other acid sensitive
funtional groups in acidic conditions.
Fehlings or benedicts solution (copper solution): blue to
red
Ketones, lacking such
an oxygen, are resistant
to oxidation.
73
Aldehydes and Ketones

Keto-enol Tautomerism:

Keto tautomer is preferred (alcohols are more
acidic than aldehydes and ketones).
74
Aldehydes and Ketones

Internal H bonding: 1,3-dicarbonlys

Enol tautomer is preferred (stabilized by
resonance and internal H-bonding)
75
Guanine, the base portion of guanosine, exists as
an equilibrium mixture of the keto and enol forms.
Which of the following structures represents the
enol form of guanine?
76
Aldehydes and Ketones

Organometallic reagents:

Nucleophilic addition of a carbanion to an
aldehyde or ketone to yield an alcohol
77
Acetoacetic Ester Synthesis
Alkyl Halide + Acetoacetic Ester  Methyl Ketone

Acetoacetic ester synthesis:


Use acetoacetic ester (ethyl acetoacetate) to
generate substituted methyl ketones
Base catalyzed extraction of α H
78
Aldehydes and
Ketones

Wolff-Kishner reduction:


Nucleophilic addition of hydrazine (H2N-NH2)
Replace =O with 2 H atoms
+ H2O
79
In which of the following reactions would
the formation of an imine occur?

a)
b)
c)
d)
Methylamine + propanol
Methylamine + propanal
Dimethylamine+ propanal
Trimethylamine + propanal
80
In which of the following reactions would
the formation of an enamine occur?

a)
b)
c)
d)
Methylamine + propanol
Methylamine + propanal
Dimethylamine+ propanal
Trimethylamine + propanal
81
In an organic chemistry class a group of
students are trying to determine the
identity of an unknown compound. In the
haloform reaction the reaction mixture
turned yellow indicating a positive result.
Which of the following is true of the
unknown compound?
a) It contains an aldehyde
b) It contains an alcohol
c) It contains a methyl ketone
d) It contains a carboxylic acid

82
Oxygen Containing
Compounds-Carboxylic Acids

Physical Properties:
 Acidic
 Trigonal planar geometry
 Higher BP and MP than alcohols
 Polarity, dimer formation in hydrogen bonding increases size and
VDW interactions
 Solubility: small (n<5) CA are soluble, larger are less soluble
because long hydrocarbon tails break up H bonding

IR absorption of C=O at ~1600, OH at ~3400

General Principles:






Acidity Increases with EWG (stabilize carboxylate)
Acidity decreases with EDG (destabilize carboxylate)
Relative reactivity
Steric effects
Electronic effects
Strain (e.g. b-lactams: 3C, 1N ring; inhibits bacterial cell wall formation)
83
Carboxylic Acids
Naming
Carboxylic acids derived from open chain
alkanes are systematically named by
replacing the terminal –e of the
corresponding alkane name with –oic acid.
Compounds that have a –CO2H group
bonded to a ring are named using the suffix
–carboxylic acid.



The –CO2H group is attached to C #1 and is not
itself numbered in the system.
84
Carboxylic Acids-important
reactions

Carboxyl group reactions:

Nucleophilic attack:

Carboxyl groups and their derivatives undergo
nucleophilic substitution.


Aldehydes and Ketones undergo addition because they lack a
good leaving group.
Must contain a good leaving group or a substituent
that can be converted to a good leaving group.
85
Carboxylic Acids-important
reactions

Reduction:


Form a primary alcohol
LiAlH4 is the reducing agent

Unlike oxidation, cannot isolate the aldehyde
CH3(CH2)6COOH
LiAlH4
CH3(CH2)6CH2OH
86
Carboxylic Acids-important
reactions

Carboxyl group reactions:

Decarboxylation:
87
Carboxylic Acids-important
reactions

Fischer Esterification Reaction:

Alcohol + Carboxylic Acid  Ester + Water


Acid Catalyzed- protonates –OH to H2O (excellent
leaving group)
Alcohol performs nucleophilic attack on carbonyl
carbon
H+
These bonds are
broken
88
Carboxylic Acidsreactions at two positions

Substitution reactions: keto reactions shown,
consider enol reactions
To make >
SOCl2
or PCl3
Heat, -H2O
R'OH, heat,
H+
-
R2NH
heat
HO89
Carboxylic Acidsreactions at two positions passage 26

Halogenation: enol tautomer undergoes
halogenation
90
Acid Derivatives- Acid Chlorides,
Anhydrides, Amides, Esters

Physical Properties:

Acid chlorides: acyl chlorides
 React violently with water
 Polar
 Dipole attractions (no H bonds)
 Higher BP and MP than alkanes, lower than alcohols

Anhydrides
 Large, polar molecules
 Dipole attractions (no H bonds)
 Higher BP than alkanes,
lower than alcohols
91
Acid Derivatives

Physical Properties:
 Amides:



Highest BP and MP
Soluble in water (H bonds)
Esters:




Poor to fair H bond acceptors
Sparingly soluble in water
Weakly basic
H on alpha C weakly acidic
92
Acid Derivatives
Naming

Acid Halides (RCOX)



Identify the acyl group and then the halide
Replace –ic acd with –yl, or –carboxylic acid with –carbonyl
Acid Anhydrides (RCO2COR’)

Symmetrical anhydrides or unsubstituted monocarboxylic acids and cyclic anhydrides of dicarboxylic acids are named
by replacing the word acid with anhydride.


Anhydrides derived from substituted monocarboxylic acids are named by adding the prefix –bis to the acid name.


Acetic acid + benzoic acid  acetic benzoic anhydride
Amides (RCONH2)

Amides with an unsubstituted –NH2 group are named by replacing the –oic acid or ic acid ending with amide, or by
replacing the –carboxylic acid ending with carboxamide.


Acetic acid  acetamide
If the nitrogen atom is further substituted, the compound is named by first identifying the substituent groups and then
the parent amide. The substituents are preceded by the letter N to identify them as being directly attached to nitrogen.


2 chloroacetic acid  bis(chloroacetic) anhydride
Unsymmetrical anhydrides- those produced from two different carboxylic acids- are named by citing the two acids
alphabetically.


2 acetic acid  acetic anhydride
Propanoic acid + methyl amine  N-Methylpropanamide
Esters (RCO2R)


Identify the alkyl group attached to oxygen and then the carboxylic acid.
Replace the –ic acid ending with -ate
93
Acid DerivativesRelative Reactivity and Reactions of
Derivatives



•Hydrolysis- +water  carboxylic
acid
•Alcoholysis- +alcohol  ester
•Aminolysis- +ammonia or amine 
amide
•Reduction- + H-  aldehyde or
alcohol
•Grignard- + Organometallic 
ketone or alcohol
A more reactive acid derivative can
be converted to a less reactive
one, but not vice versa
Only esters and amides commonly
found in nature.
Acid halides and anhydrides react
rapidly with water and do not exist
in living organisms
94
Acid Derivatives-important
reactions

Preparation: replace OH

Nucleophilic Substitution:
95
Acid Derivatives
Hoffman Degredation


Hoffman degradation (rearrangement) of amides; migration of an aryl
group
1° Amides + Strong basic Br or Cl soln  1° Amines + CO2
http://users.ox.ac.uk/~mwalter/web_04
96
/resources/name_reactions/hofmann.s
html
Acid Derivatives
Transesterification


Transesterification: exchange alkoxyl group
with ester of another alcohol
Alcohol + Ester  Different Alcohol +
Different Ester
97
Acid DerivativesSaponification

Saponificationester hydrolysis in
basic solutions
98
Acid DerivativesHydrolysis of Amides

passage 33
Hydrolysis of amides:

Acid or base catalyzed
99
Acid Derivatives
Strain (e.g., β-lactams)





Lactams- cyclic amides
Although amides are most stable acid derivative, β-lactams are highly
reactive due to ring strain.
Subject to nuclephilic attack.
Found in several types of antibiotics
Inhibits bacterial cell wall formation.
100
Keto-Acids and Esters


Keto acids contain a ketone and a carboxyl group (alpha
and beta)
Amino acids degraded to alpha keto acids and then go
into the TCA

Esters have distinctive odors and are used as artificial
flavors and fragrances
Beta-keto esters have an acidic alpha hydrogen

Consider keto-enol tautomerism


Naming Esters
 Esters are named by first determining the alkyl
group attached to the oxygen and then the
carboxylic acid from which the ester is derived.
 EX: Methyl Propanoate is derived from
propanoic acid and a methyl group
101
Keto Acids and Estersimportant reactions

Decarboxylation

Acetoacetic ester synthesis: see aldehydes
and ketones
102
Amines



Important functions in amino acids, nucleotides, neurotransmitters
1o, 2o, 3o, 4o based on how many carbons bonded to
Can be chiral, rarely have 4 side groups
103
Amines









Important functions in amino acids, nucleotides, neurotransmitters
1o, 2o, 3o, 4o based on how many carbons bonded to
Can be chiral, rarely have 4 side groups
Physical properties:
Polar
Similar reactivity to alcohols
Can H bond, but weaker H bond than alcohols
MP and BP higher than alkanes, lower than alcohols
IR absorption: 2800-3000
104
Amines













Important functions in amino acids, nucleotides, neurotransmitters
1o, 2o, 3o, 4o based on how many carbons bonded to
Can be chiral, rarely have 4 side groups
Physical properties:
Polar
Similar reactivity to alcohols
Can H bond, but weaker H bond than alcohols
MP and BP higher than alkanes, lower than alcohols
IR absorption: 2800-3000
General principles:
Lewis bases when they have a lone electron pair

NR3 > NR2 > NR > NH3 (least basic)
Stabilize adjacent carbocations and carbanions
Effect of substituents on basicity of aromatic amines:

Electron withdrawing are less basic
105

Electron donating are more basic
Amines-major reactions

Amines are basic and fairly nucleophilic

Amide formation: proteins
106
Amines-major reactions

Reactions with nitrous acid (HONO):

Distinguishes primary, secondary, and tertiary
Primary: burst of colorless, odorless N2 gas

Secondary: yellow oil, nitrosamine-powerful carcinogen

Tertiary: colorless solution, amine forms an ion, e.g.
(CH3)3NH+

107
Amines- Alkylation

 Alkylation: SN2 with amine as the nucleophile and alkyl halides as
the electrophile

Reaction with 1° alkyl halide

Alkylation of 1° and 2° are difficult to control and often lead to mixtures
of products

Alkylation of 3° amines yield quaternary ammonium salts
108
AminesHoffman Elimination

Elimination of amine as a quaternary ammonium salt to
yield an alkene.

Does not follow Zaitsev’s rule.

Less highly substituted alkene predominates
109
For Next Time…
Last Slide (Hooray!!!!)




Functional Group Quiz
Spectra
Separations and Purifications
Biological Molecules




Carbohydrates
Amino acids and proteins
Lipids
Phophorous containing compounds
110